A recent study supported by the National Institute on Drug Abuse (NIDA) indicates that frequent consumption of addictive drugs such as cocaine produces long-term effects in areas of the brain associated with motivation and reward. However, the specific process of those transformations is still unclear. The results of the study published this week in the journal Neuron provide further understanding of the essential process and effects of cocaine on the composition and function of the genome, the entire arrangement of DNA information in order to create an organism.
“This study’s findings enable us to glimpse for the first time exactly how cocaine modifies the activity of genes in regions of the brain that mediate reward,” explains NIDA Director Dr. Nora Volkow. “In addition, this research has identified a novel family of genes that appear to play a key role in the brain’s response to cocaine. These genes represent promising new targets for the development of medications to treat cocaine addiction.”
In order to examine the changes in gene activity in the brains of laboratory mice injected with cocaine, a group of scientists headed by Eric Nestler, M.D., Ph.D., of Mount Sinai School of Medicine in New York, used an innovative powerful molecular analysis technique called ChIP-chip. These alterations are changes in proteins known as histones and transcription factors. They connect to DNA and control the mechanism by which the genetic information in a strand of DNA is interpreted and used in the creation of a corresponding sequence of RNA. Within the cell, a translation process uses the information in the RNA sequence to generate the ending protein products.
“Using these markers of gene activity, we mapped the genomic effects of chronic cocaine use in the nucleus accumbens, which is a key component of the brain’s reward circuitry,” remarks Dr. Nestler. “This analysis provides fundamentally new information about the range of genes that are altered by cocaine in this brain region. For example, this study demonstrated, for the first time, that a family of genes called the sirtuins are activated in the nucleus accumbens by chronic cocaine administration and contribute to addiction-related behaviors in animal models.”
“We showed that blocking the activity of the sirtuins specifically in the nucleus accumbens reduced both cocaine’s rewarding effects and the motivation to self-administer the drug,” explains Dr. Nestler. There is a vast potential of development in using sirtuin inhibitors as treatment agents for cocaine addiction, according to the findings. In order to discover further therapeutic targets for cocaine dependence, additional investigation of other genes activated and inhibited by cocaine may be needed.
The study was the work of Dr. Nestler and his collaborators at the University of Texas Southwestern Medical Center at Dallas and Florida State University in Tallahassee.
The National Institute on Drug Abuse is part of the National Institutes of Health, U.S. Department of Health and Human Services.
Written by Stephanie Brunner (B.A.)